Administration of endotoxin to humans allows a unique way to evaluate the early inflammatory reactions that occur during infection. Characterizing these responses and the mechanisms that control them is important because these inflammatory responses contribute to the development of septic shock and organ failure. Under protocol 92-CC- 0141, the effects of direct instillation of endotoxin into lung sub- segments will be evaluated. Sequential bronchoalveolar lavage will be performed at 2, 6, 24, or 48 hours after endotoxin instillation. Analyses will include the following: (1) bronchoal-veolar lavage for acute phase cytokines (e.g., tumor necrosis factor, interleukin-1 (IL- 1), IL-8, and activated proteases (e.g., elastase, plasminogen, metalloproteases); (2) flow cytometry of neutrophils and lymphocyte subpopulations; (3) determination of cytokine receptors including type I and II tumor necrosis factor receptors and IL-1 receptors in lavage and on elicited neutrophils; (4) apoptosis of neutrophils following their recruitment into the distal airways; and (5) systemic effects including acute phase cytokine release, recruitment of cells from the marrow, and the initiation of acute phase protein release. These observations will be useful in defining important events in the initiation and resolution of acute lung inflammation to bacterial endotoxin.

Agency
National Institute of Health (NIH)
Institute
Clinical Center (CLC)
Type
Intramural Research (Z01)
Project #
1Z01CL000171-04
Application #
6289406
Study Section
Special Emphasis Panel (CCMB)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Clinical Center
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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Luca, Rudolf; Lijnen, H Roger; Suffredini, Anthony F et al. (2002) Increased angiostatin levels in bronchoalveolar lavage fluids from ARDS patients and from human volunteers after lung instillation of endotoxin. Thromb Haemost 87:966-71
O'Grady, N P; Preas, H L; Pugin, J et al. (2001) Local inflammatory responses following bronchial endotoxin instillation in humans. Am J Respir Crit Care Med 163:1591-8